Xin Wan

MicroRNA-203 inhibits the proliferation and invasion of U251 glioblastoma cells by directly targeting PLD2

MicroRNAs (miRNAs) have been demonstrated to be important in the development and progression of various types of cancer. However, the exact roles of certain anti‑oncogenic miRNAs in human malignant gliomas remain to be elucidated. The present study aimed to reveal the expression of microRNA‑203 (miR-203) in normal brain tissues and gliomas, and to investigate the role of miR-203 in cell proliferation and migration in human glioblastoma U251 cells. Real-time reverse transcription polymerase chain reaction (RT-PCR) showed that the expression of miR-203 in high WHO grade glioma tissues was significantly decreased compared with low WHO grade glioma tissues and normal brain tissues, and its expression demonstrated a decreasing tendency with ascending WHO grades. The transfection of the miR-203 mimic into U251 cells markedly downregulated the expression of phospholipase D2 (PLD2), which was identified as a direct target of miR-203. Furthermore, miR-203 overexpression significantly suppressed the proliferation and invasion of U251 cells, while the overexpression of PLD2 abrogated these effects induced by the miR-203 mimic. In conclusion, the present study demonstrated the clinical significance of miR-203 in gliomas and suggested that miR-203 was able to inhibit the proliferation and invasion of glioma cells, partially at least via suppressing the protein expression of PLD2. Thus, miR-203 may be a novel candidate for the development of therapeutic strategies for gliomas.

PAX6, a novel target of miR-335, inhibits cell proliferation and invasion in glioma cells

Paired box 6 (PAX6), a highly conserved transcription factor, is important in glioma. However, the molecular mechanisms involved remain unclear. The present study demonstrated that the expression of PAX6 was significantly reduced with the malignancy of glioma and also identified PAX6 as a novel target of microRNA (miR)‑335, which was significantly upregulated in glioma. The inhibition of miR‑335 increased the protein expression of PAX6, whereas the upregulation of miR‑335 suppressed its expression in human glioma U251 and U87 cells. Furthermore, upregulation of miR-335 promoted U251 cell proliferation, colony formation and invasion, which was reversed by the overexpression of PAX6. Furthermore, the present study demonstrated that the effect of miR‑335 on U251 cell invasion was via the modulation of matrix metalloproteinase (MMP)‑2 and MMP‑9 expression by targeting PAX6. In conclusion, the present study demonstrated that PAX6, as a novel target of miR‑335, has an anti‑oncogenic function in glioma, and thus PAX6 may serve as a therapeutic target for glioma.

MicroRNA-663 inhibits the proliferation, migration and invasion of glioblastoma cells via targeting TGF-β1

Cell migration and invasion are key processes involved during tumor metastasis. Recently, microRNAs (miRs) have been demonstrated to play important roles in the regulation of cancer metastasis. However, the underlying mechanisms remain unknown. Here, we aimed to investigate the exact role of miR-663 in the metastasis of glioblastoma as well as the underlying mechanisms. By performing quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis, we demonstrated that miR-663 was significantly downregulated in glioblastoma tissues (n=25), when compared to that in normal brain tissues (n=15). In addition, its expression levels were also reduced in human glioblastoma cell lines, A172 and U87. Furthermore, restoration of miR-663 expression led to a significant decrease in the cell proliferation, migration and invasion of human glioblastoma A172 and U87 cells. We further identified TGF-β1 as a direct target of miR-663, and found that the expression of TGF-β1 was negatively mediated by miR-663 at the post-transcriptional level in glioblastoma cells. Moreover, overexpression of TGF-β1 significantly reversed the inhibitory effects of miR-663 upregulation on the proliferation, migration and invasion in A172 and U87 cells. In addition, our data suggest that MMP2 and E-cadherin, a key factor in epithelial-mesenchymal transition (EMT), are involved in the miR-633/TGF-β1-mediated metastasis of glioblastoma. In summary, miR-663 plays an inhibitory role in the regulation of proliferation, migration and invasion of glioblastoma cells, partly at least, via direct mediation of TGF-β1 as well as downstream MMP2 and E-cadherin. Therefore, we suggest that miR-663 is a potential candidate for the prevention of glioblastoma metastasis.

Study of cell apoptosis in the hippocampus and thalamencephalon in a ventricular fluid impact model

The aim of this study was to investigate the apoptosis of nerve cells in the hippocampal and thalamencephalon regions using a rabbit model of ventricular fluid impact. The results for the study demonstrated a variety of pathophysiological changes in the rabbit model, while changes in the hippocampal and thalamencephalon regions were observed under a light microscope following hematoxylin and eosin (H&E)/terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. Among the mild, moderate and severe injury groups, there were significant differences in the mortality rate and in the changes in vital signs and consciousness recovery time following trauma. Furthermore, H&E staining showed that pathological changes, such as hemorrhage and necrosis, occurred in the hippocampal and thalamencephalon regions at an early stage subsequent to trauma, while TUNEL staining showed that neuronal apoptosis occurred in the various injury groups. In traumatic brain injuries, the impact caused by cerebrospinal fluid moving with a certain energy results in marked damage to the contralateral periventricular structures and may generate a series of pathophysiological changes.

Role of miR-223/paired box 6 signaling in temozolomide chemoresistance in glioblastoma multiforme cells

Glioblastoma (GBM) is the predominant and most fatal type of brain tumor in adults. The prognosis of GBM remains poor despite advances in surgery, chemotherapy and radiotherapy. It is common that patients with GBM exhibit innate or acquired resistance to temozolomide (TMZ), a standard chemotherapeutic agent for GBM, and a previous report demonstrated that miRNA-233 (miR-223) promotes the growth and invasion of GBM cells by targeting tumor suppressor paired box 6 (PAX6). The present study explored the effect of TMZ on miR-223/PAX6 signaling in addition to the effect of miR-223/PAX6 signaling on TMZ chemoresistance in human GBM cells. Luciferase reporter assays confirmed that miR-223 directly targets PAX6 through binding to its 3′-untranslated region. TMZ reduced the expression level of miR-223 in a concentration-dependent manner in U251 and U118 GBM cells, which led to increased expression of PAX6. miR-223 and/or PAX6 were overexpressed and knocked down in U251 and U118 cells, and the half maximal inhibitory concentration (IC50) of TMZ and cell proliferation under TMZ treatment were used as measures of TMZ chemoresistance. The results demonstrated that overexpression of miR-223 in GBM cells markedly decreased TMZ-induced inhibition of cell proliferation and increased TMZ IC50, which could be abolished by overexpression of PAX6. On the other hand, knocking down miR-223 in GBM cells with antagomir significantly enhanced the inhibitory effect of TMZ on GBM cell proliferation and decreased the TMZ IC50, which could be abolished by knockdown of PAX6. In conclusion, the present study demonstrated that TMZ inhibits GBM cell proliferation by inhibiting the expression of miR-223, which leads to increased expression of tumor suppressor PAX6. Overexpression of miR-223 increases TMZ chemoresistance, while inhibition of miR-223 with antagomir markedly decreases TMZ chemoresistance in GBM cells. The present study provided novel insight into the molecular mechanisms underlying the pharmacological effects, in addition to the chemoresistance, of TMZ for GBM.

Diagnosis and treatment of cystic meningioma

OBJECTIVE To explore the pathogenetic mechanism of cystic meningioma and the key to its diagnosis and operation. METHODS Clinical data of 8 patients with cystic meningioma were analyzed retrospectively. The occuring position and cure rate of cystic meningioma were compared with those of solid meningioma in the corresponding period. RESULTS All patients were subjected to total resection of tumor parenchyma and cystic wall. No operative death and severe complications occurred. The incidence of uppertentorial region of cystic meningioma was higher than that of solid meningioma, and the difference was significant (χ(2)=2.618, P<0.05). The cure rate was not significantly different between cystic meningioma and solid meningioma (χ(2)=0.010, P>0.05). CONCLUSION Removing tumor totally is the key to preventing its recurrence.

Minimally Invasive Surgery is Superior to Conventional Craniotomy in Patients with Spontaneous Supratentorial Intracerebral Hemorrhage: A Systematic Review and Meta-Analysis

BACKGROUND Outcomes of minimally invasive surgery (MIS) versus conventional craniotomy (CC) for patients with spontaneous supratentorial intracerebral hemorrhage (SICH) have not been compared previously. We reviewed the current evidence regarding the safety and efficacy of MIS compared with CC in patients with SICH. METHODS We conducted a meta-analysis of studies comparing MIS and CC in patients with computed tomography-confirmed SICH published between January 2000 and April 2018 in MEDLINE, Embase, and the Cochrane Controlled Trials Register based on PRISMA inclusion and exclusion criteria. Binary outcomes comparisons between MIS and CC were described using odds ratios (ORs). RESULTS Five randomized controlled trials (RCTs) and 9 prospective controlled studies (non-RCTs), involving a total of 2466 patients, met our inclusion criteria. There was a statistically significant difference in mortality rate between MIS and CC (OR, 0.76; 95% confidence interval [CI], 0.60-0.97). MIS was associated with a lower rate of rebleeding (OR, 0.42; 95% CI, 0.28-0.64) and a higher rate of good recovery compared with CC (OR, 2.27; 95% CI, 1.34-3.83). CONCLUSIONS Patients with SICH may benefit more from MIS than CC. Our study could help clinicians optimize treatment strategies in SICH.